Abstract

Athletic performance is a polygenic trait influenced by both environmental and genetic factors.¹ Genetics has a great influence over athletic performance such as strength, power, muscle fibre, flexibility and other phenotypes. HIF1A (hypoxia inducible factor 1 alpha), a master-regulator of oxygen-homeostasis, plays crucial roles in cellular metabolism.² HIF1A regulates expression of nearly all enzymes involved in glycolysis. HIF1A mediates oxygen delivery to cells as well as allows cells to survive under oxygen deprivation by regulating expression of hundreds of genes involved in angiogenesis, erythropoiesis glucose metabolism and transport.^2,3 The HIF1A gene is considered as a genetic marker of athletic ability because of its proposed role in shifting of oxidative type muscle fibres to glycolytic type and increasing hypoxia resistance to the cells.⁴ The aim of this study was to perform a meta-analysis of all available case-control-studies of athletes to systematically summarise the association between HIF1A C1772T (rs11549465) polymorphism and athletic performance.

Literature-mining was performed for the last 15 years using PubMed and Google Scholar to retrieve relevant case-control studies. Odds ratio (OR) with 95% confidence intervals (CIs) were calculated using fixed or random effects model incorporating inverse-variance-weighted method for relating HIF1A 1772 C/T polymorphism (rs11549465; which results in Pro582Ser substitutions) with elite athlete’s performance. In subgroup analyses top-level athletes were considered as ‘elite athletes’ who were competing in the Olympics Games &/World and European championships and won medals; and ‘other athletes’ being national level and regional competitors with no less than four years of experience participating in their sport. The distributions of genotypes in the controls were checked for HWE. Further subgroup-analysis of HIF1A 1772 C/T was carried out by ethnicity.

A meta-analysis of 19 studies comprising 1616 cases and 9253 controls was conducted to identify the association of HIF1A rs11549465 (C/T) polymorphism with elite athlete’s performance. Results demonstrated that the T allele is significantly associated with elite athletes under three genetic models (TT+CT vs CC: OR = 1.73, 95% CI: = 1.22–2.46, p 0.002); (CT vs CC: OR = 1.73, 95% CI: = 1.21–2.47, p 0.003); (T vs C: OR = 1.64, 95% CI: = 1.19–2.25, p 0.002) whereas other athletes group showed no significant associations (TT+CT vs CC: OR = 1.44, 95% CI: = 0.72–2.88, p 0.30); (CT vs CC: OR = 1.37, 95% CI: = 0.65–2.89, p 0.40); (T vs C: OR = 1.38, 95% CI: = 0.84–2.29, p 0.20). For elite athletes no significant heterogeneity was observed (T vs C: I^2 = 60.8% [0% - 86.9%]; Q = 7.6; p 0.054). For Caucasian population, sub-group analyses data suggested that the HIF1A 1772 C/T polymorphism is highly associated with athletic performance in three models (TT+CT vs CC: OR = 1.51, 95% CI: = 1.15–1.98, p 0.003); (CT vs CC: OR = 1.53, 95% CI: = 1.17–2.01, p 0.002); (T vs C: OR = 1.41, 95% CI: = 1.1–1.80, p 0.005).

Results from this study revealed that HIF1A C1772T polymorphism is significantly associated with elite athletes compared with controls or other athletes. This suggests that the T allele variant could be one of the factors influencing the power athletic performance.